Interaction between human papillomavirus type 5 E2 and polo-like kinase 1.

The E2 protein of the papillomavirus plays an essential role in the viral life cycle. Through a yeast two-hybrid screening, human polo-like kinase 1 was found to interact with human papillomavirus type 5 E2. Further characterization identified that the domains responsible for the interaction are the transactivation domain of HPV-5 E2 and the sequence between the kinase and the polo box domains of Plk1. In vivo, Plk1 and HPV-5 E2 are colocalized at the nuclear speckles. In the skin epithelium not infected with epidermodysplasia verruciformis associated HPVs, Plk1 is expressed in the stratum basale, indicating that the Plk1-HPV-5 E2 interaction likely occurs in the keratinocytes at the basal layer of the epithelium upon infection of HPV-5. Both HPV-5 E2 and Plk1 also interact with the E2 binding domain of Brd4. The E2 binding domain of Brd4 is phosphorylated by Plk1 in vitro, and this phosphorylation event is blocked by the presence of HPV-5 E2. Hence, these findings suggest the possibility that the cellular function of Brd4 is de-regulated by forming a complex with HPV-5 E2 in the infected epithelial cells. Copyright 2009 Wiley-Liss, Inc.